Modulation of Neuropathic Pain by Endocannabionid Signalling
Ildikó
Rácz1*,
Xavier
Nadal2,
Judith
Alferink1, 3,
Josep
E.
Banos2,
Jennifer
Rehnelt1,
Miquel
Martín2,
Alfonso
G.
Adan4,
Elena
Sanguino5,
Jorge
Manzanares5,
Andreas
Zimmer1 and
Rafael
Malach2
-
1
Institute of Molecular Psychiatry, Germany
-
2
Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Spain
-
3
Department of Psychiatry, University of Bonn, Germany
-
4
Instituto Nacional de Investigación y Tecnología Agraria, Departamento de Reproducción Animal y Conservación de Recursos Zoogenéticos, Spain
-
5
Universidad Miguel Hernández-CSIC, Spain
Neuropathic pain develops as a consequence of peripheral nerve injury. Because it is difficult to treat there is a great medical need for novel pharmacotherapies. Recent studies suggest that CB2 selective ligands seem to be effective in animal models of neuropathic pain. In this study, we have investigated CB2 mediated mechanisms in the modulation of neuropathic pain. We used genetically modified mice lacking or overexpressing cannabinoid CB2 receptors to evaluate the contribution of these receptors in the development of neuropathic pain. We performed partial sciatic nerve ligation followed by nocicepive, histological and expression profiling studies. INF- and CB2 receptor double knockout mice, as well as irradiated wild type mice receiving bone marrow transplantation from CB2 knockout animals were used to address the role of inflammatory responses. CB2 knockout animals subjected to a partial nerve injury developed mechanical allodynia and thermal hyperalgesia to a similar extend as wild type control animals on the ipsilateral side of the nerve injury. However, they also displayed increased pain sensitivity on the contralateral side. Transgenic mice overexpressing CB2 receptors had attenuated neuropathic pain responses. Expression profiling studies revealed an enhanced INF- response in the absence of CB2 receptors. Analysis of double knockout animals confirmed that the enhanced INF- response caused the expansion of the hyperalgesic area in the absence of CB2 receptors. These results suggest that CB2 mediated mechanisms contribute to the local containment of the hyperalgesic response after peripheral nerve injury. CB2 receptors thus represent an interesting therapeutic target for the treatment of neuropathic pain.
Conference:
12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009.
Presentation Type:
Poster Presentation
Topic:
Pathophysiology and neurology - non-degenerative disorders
Citation:
Rácz
I,
Nadal
X,
Alferink
J,
Banos
JE,
Rehnelt
J,
Martín
M,
Adan
AG,
Sanguino
E,
Manzanares
J,
Zimmer
A and
Malach
R
(2009). Modulation of Neuropathic Pain by Endocannabionid Signalling.
Front. Syst. Neurosci.
Conference Abstract:
12th Meeting of the Hungarian Neuroscience Society.
doi: 10.3389/conf.neuro.01.2009.04.039
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Received:
27 Feb 2009;
Published Online:
27 Feb 2009.
*
Correspondence:
Ildikó Rácz, Institute of Molecular Psychiatry, Bonn, Germany, iracz@uni-bonn.de